title: Identification and Validation of a Putative Polycomb Responsive Element in the Human Genome.
abstract: Epigenetic cellular memory mechanisms that involve polycomb and trithorax group of proteins are well conserved across metazoans. The cis-acting elements interacting with these proteins, however, are poorly understood in mammals. In a directed search we identified a potential polycomb responsive element with 25 repeats of YY1 binding motifthatwe designate PRE-PIK3C2B as it occurs in the first intron of human PIK3C2B gene. It down regulates reporter gene expression in HEK cells and the repression is dependent on polycomb group of proteins (PcG). We demonstrate that PRE-PIK3C2B interacts directly with YY1 in vitro and recruits PRC2 complex in vivo. The localization of PcG proteins including YY1 to PRE-PIK3C2B in HEK cells is decreased on knock-down of either YY1 or SUZ12. Endogenous PRE-PIK3C2B shows bivalent marking having H3K27me3 and H3K4me3 for repressed and active state respectively. In transgenic Drosophila, PRE-PIK3C2B down regulates mini-white expression, exhibits variegation and pairing sensitive silencing (PSS), which has not been previously demonstrated for mammalian PRE. Taken together, our results strongly suggest that PRE-PIK3C2B functions as a site of interaction for polycomb proteins.
authors.affiliation: Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, India.
authors.forename: Hemant
authors.initials: H
authors.lastname: Bengani
authors.forename: Shweta
authors.initials: S
authors.lastname: Mendiratta
authors.forename: Jayant
authors.initials: J
authors.lastname: Maini
authors.forename: Dasari
authors.initials: D
authors.lastname: Vasanthi
authors.forename: Hina
authors.initials: H
authors.lastname: Sultana
authors.forename: Mohsen
authors.initials: M
authors.lastname: Ghasemi
authors.forename: Jasmine
authors.initials: J
authors.lastname: Ahluwalia
authors.forename: Sowmya
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Mishra
authors.forename: Vani
authors.initials: V
authors.lastname: Brahmachari
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D058541:Class II Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D004330:Drosophila; D015894:Genome, Human / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D007438:Introns / Q000502:physiology*; D009363:Neoplasm Proteins; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology*; D014157:Transcription Factors; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; C430461:SUZ12 protein, human; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D063151:Polycomb Repressive Complex 2; D058541:Class II Phosphatidylinositol 3-Kinases; C502616:PIK3C2B protein, human